Microfluidic lab-on-a-chip (LOC) systems are stated to revolutionize the healthcare industry by replacing large-scale chemistry/biology laboratories with hand-held automated diagnostic tools, bringing sophisticated diagnostic techniques to patients' homes and third world countries. The LOC systems' capacity to handle and analyze minute sample volumes in the femtoliter to picoliter range and ability to test hundreds of samples simultaneously extends tremendous potential for areas like drug discovery and remote healthcare. Small, e.g. credit card-sized or smaller, self-contained LOC devices are expected to make complex medical diagnoses easy to perform.
One important component of sophisticated LOC devices is the microfluidic pump, which moves a liquid sample between the various mixers, separators, reactors and detectors required to perform an analysis. The ease-of-manufacture and small size of electrokinetic pumps, e.g. electroosmotic (EO) pumps, are advantages for their use as microfluidic pumps in LOC systems.
However, electrokinetic pumps usually produce gas bubbles; e.g. hydrogen gas, oxygen gas, hydrogen peroxide and/or protons (acid) or hydroxide ions (base), at the pump electrodes due to electrochemical reactions in the electrolyte when an electrical field is applied to the electrolyte. Such electrochemical reactions are undesirable. Gases, when generated, can quickly break the electrical connection between the liquid sample, e.g. an aqueous sample, and the electrode, affecting the mobility of the liquid sample within the electrokinetic pump. Further, generated acid, base and/or hydrogen peroxide can disturb or destroy the sensitive sample materials, e.g. proteins, to be studied.
The problem with today's electrokinetic pumps stems from the metal electrodes used to apply and maintain an electric field in the electrolyte. Maintaining an electric field in an electrolyte requires electrochemistry to be performed in or on the electrolyte at the pump electrodes, effectively transducing the current from electronic to ionic charge carriers or vice versa. These electrochemical processes often consume the electrolyte, e.g. water, itself, producing electrochemical by-products, such as H+, OH−, H2O2, H2 gas and O2 gas in the case of the electrolyte being water, which by-products can be detrimental to sensitive biological or chemical sample materials being transported or separated. In the specific case of microfluidic devices, the production of H2 or O2 gas at a pump electrode can create a bubble which, eventually, blocks liquid from reaching the pump electrode and renders the microfluidic device useless. Further, the formation of H+, OH− may change the pH of the electrolyte at the pump electrodes which may negatively affect the sample material to be studied. Furthermore, the electrochemical reaction may cause consumption of, or otherwise disturb the environment of, the reagents or analyte used.
The state-of-the-art for LOC devices of today offers three alternatives to solve the above-mentioned problems.
A first proposed solution uses an external pump. However, the external pump is often considerably larger than the LOC itself, and thereby precluding a self-contained device.
In a second proposed solution, an internal mechanical pump, such as an electro-mechanical, pneumatic or hydraulic pump, is used. However, such internal mechanical pumps are often very expensive to manufacture.
According to a third proposed solution, an internal electroosmotic pump is used. An advantage with the internal electroosmotic pump is that it has no moving parts, and is therefore easy to manufacture.
Unfortunately, as previously described, internal electroosmotic pumps usually generate unwanted by-products in the electrolyte at the pump electrodes which impede their application in a LOC device or negatively impact the sample to be tested. The side reactions generating these unwanted by-products can be mediated by adding a chemical buffer, e.g. a buffer to keep the pH at a desired level, to the solutions to be pumped, to a sample to be tested, separated, or to a carrier electrolyte. However, these chemicals can sometimes interfere with the materials being studied or transported, and are therefore undesirable. Further, the use of a buffer implies an additional cost for manufacturing and operating the device.
Alternatively, very large volume containers surrounding the metal electrodes can minimize the impact of the by-products through dilution. However, this alternative is undesirable in microfluidic LOC devices due to the size of the large volume containers and due to the size requirements on LOC devices.
In another alternative, a metal that can be oxidized and dissolved in solution (such as Ag, etc.) is used in one or both electrodes. The metal is oxidized at the positive electrode and released into solution as a cation, which is transported with the fluid in the pump to the negative electrode, where it is reduced again. The challenge with this type of system is the sensitivity of biological samples and proteins to the Ag cation. For example, a Ag cation is often toxic to bacteria or living cells.
The US application U.S. patent application Ser. No. 11/168,779, published as US 2007/0009366 A1, to Myers et al., describes an electroosmotic pump wherein the problem of gas bubble formation is overcome by providing a sheath around at least one of the electrodes. The sheath being configured to pass ions, to reduce the passage of gas bubbles formed at the electrode and to collect the formed gas bubbles inside the sheath. Further, when the gas pressure is built up within the sheath, the gas bubbles are discarded from the electroosmotic pump.
The U.S. Pat. No. 6,287,440 B1, to Sandia Corporation, discloses a method and an apparatus for eliminating electrokinetic pump failure caused by gas bubbles formed by electrochemical decomposition of an electrolyte thereby blocking current flow through the electrokinetic pump. In the method and apparatus disclosed in U.S. Pat. No. 6,287,440 B1, the electrodes are placed away from the pressurized region of the pump, such that gas generated at the electrodes can escape into a larger buffer reservoir and not into the high pressure region of the pump where the gas bubbles can interrupt current flow.
The US application U.S. patent application Ser. No. 11/102,063, published as US 2005/0189225 A1, to Liu et al., describes a microfluidic system comprising an electroosmotic flow pumping means having a bubble-free electrode to prevent electrolysis and bubble formation. The bubble-free electrode comprises a tube loaded with an immobilized polymer and provides a means to apply voltage across pump channels while preventing passages of fluid through it, and a means to avoid electrolysis and bubble formation in or close to the microfluidic channels.
Drawbacks with these types of electrokinetic pumps are that they are difficult to include in a miniaturized device as they often requires a larger footprint. Furthermore, the complex geometries required and use of several different materials complicate their manufacture. Further drawbacks are bubbles generated at the pumping electrodes, as well as changes in pH caused by hydrolysis.
The present invention aims to overcome the drawbacks of the prior art electrokinetic fluid systems and to provide an electrokinetic fluid system suitable for a micofluidic lab-on-a-chip (LOC) system.